It depends what exactly it is you're asking
If you're trying to update an existing app, then it may or may not update depending on what the reason for the new version being "unavailable" on your device is. If it's just because they've stopped serving your region from the play store, for example, the updated app should side-load without any issues. If the new apk has a hard requirement, such as needing a higer version of Android than your device has, the the install will fail.
If your asking if Play Store will continue to install updates after side-loading a app that unsupported from the Play store then, no, you'll need to keep installing updates manually, I believe